Liquid Metal Nanoplatform Based Autologous Cancer Vaccines.

Abstract

Therapeutic cancer vaccines have been vigorously sought to bolster host adaptive immunity against metastatic cancers, but tumor heterogeneity, ineffective antigen utilization, and immunosuppressive tumor microenvironment hinder their clinical applications. Autologous antigen adsorbability and stimulus-release carrier coupling with immunoadjuvant capacity are urgent for personalized cancer vaccines. Here, we propose a perspective strategy of using a multipotent gallium-based liquid metal (LM) nanoplatform for personalized in situ cancer vaccines (ISCVs). The antigen-capturing and immunostimulatory LM nanoplatform can not only effectively destroy orthotopic tumors to generate multifarious autologous antigens upon external energy stimulation (photothermal/photodynamic effect) but also capture and transport antigens into dendritic cells (DCs) to enhance antigen utilization (adequate DCs uptake, antigen-endo/lysosomal escape) and facilitate DCs activation (mimic alum immunoadjuvant capacity), which ultimately awaken systemic antitumor immunity (expand cytotoxic T lymphocytes and modulate tumor microenvironment). With immune checkpoint blockade (anti-PD-L1) to further relieve the immunosuppressive tumor microenvironment, the positive tumoricidal immunity feedback loop was established to effectively eliminate orthotopic tumors, inhibit abscopal tumor growth, relapse, and metastasis as well as tumor-specific prevention. Collectively, this study demonstrates the potential of a multipotent LM nanoplatform for personalized ISCVs, which will open frontier exploration of LM-based immunostimulatory biomaterials and may encourage further investigation of precise individualized immunotherapy.